The overall objective of taste research is to understand how the mammalian gustatory system encodes information from the taste cells, through the peripheral nerve to the taste cortex, and to determine what key mechanisms participate in this process. While the ultimate target species for understanding these mechanisms is the human, it is essential to use a well-defined animal mode to elucidate them. We propose to use mouse, the genetically defined animal model. The objective of this application is to characterize taste sensitivity in C57BLJ6 (B6) and alpha-gustducin knockout mice as completely as possible and compare distribution of mechanisms throughout the tongue in much greater detail than is currently available. These data will form the basis which will help to localize and predict changes in the taste system caused by genetic manipulations. The central hypothesis of this application is that the multiple mechanisms involved in sweet and bitter taste transduction are not distributed uniformly throughout the tongue. In this application we are going: 1) To study concentration-response functions of the whole chorda tympani and glossopharyngeal nerves for 24 compounds in B6 mice. 2) To reveal differences in responses to bitter or sweet compounds in different populations of taste buds by comparison of the response profiles of single fibers in two nerves in B6 mice. 3) To find whether responses mediated by alpha-gustducin are affected differently in the anterior and posterior regions of the tongue in alpha-gustducin knockout mice. This will be done by comparison of distributions of different types of the single fibers and their response profiles in the different populations of the taste buds in alpha-gustducin knockout and wild type mice. The rationale behind the proposed research is based on our recordings from both chorda tympani (CT) and glossopharyngeal (NG) nerves in B6 strain and genetically manipulated a-gustducin knockout mice. In wild-type B6 mice we found differences in sensitivities of the two nerves for stimuli belonging not only to different taste qualities, such as bitter and sweet, but for stimuli of the same taste quality. Comparisons between alpha-gustducin knockout mice and wild type siblings showed that these genetic manipulations altered responses in the CT and the NG differently. Using unique and advanced technique to acquire data simultaneously from several single taste fibers and separate them off-line, and an extended array of taste stimuli, we expect to find that different compounds, which are bitter and sweet to humans, elicit specific patterns of responses in these two major taste nerves. This will reveal different distributions of the mechanisms involved in bitter and sweet taste in the taste buds of fungiform, foliate, and circumvallate papillae.